captopril were cough, taste abnormally, dizziness or hypotension.
Calculations suggest that a reduction in mortality could be
achieved without side effects after treating only 24 patients.^4 Yet
nearly 200 patients would have to be treated before encountering
one case in which side effects were found without a mortality
benefit. This makes ACE inhibition a very safe form of therapy.
Do AT1-receptor blockers confer the same advantages?
These agents are not currently (1999) licenced for use in heart
failure in the USA nor in the UK. There are some key theoretical
differences from ACE inhibitors, such as decreased breakdown
of the protective vasodilator bradykinin during ACE inhibition,
versus the likelihood that AT1 blockade gives more complete
inhibition of the renin-angiotensin system than does ACE
inhibition. The ELITE II trial showed losartan to be no more
effective than captopril in reducing mortality in the elderly. In
the subgroup of patients taking beta blockers, mortality
decreased in those taking captopril, compared with losartan.
ACE inhibitors, therefore, remain the cornerstone of the therapy
of heart failure.^5
It should be noted that data support the use of spironolactone
administration (25mg/day) in those with severe heart failure.
Concerns about hyperkalaemia relating to concomitant use with
ACE inhibition were generally unfounded in this study, although
potassium levels in the order of 6mmol/l were accepted.^6
RReeffeerreenncceess
1 Hall AS, Murray GD, and Ball SG. Follow-up study of patients
randomly allocated ramipril or placebo for heart failure after acute
myocardial infarction: AIRE Extension (AIREX) Study. Acute
Infarction Ramipril Efficacy. Lancet1997; 334499 : 1493–7.
2 The SOLVD Investigators. Effects of enalapril on mortality and the
development of heart failure in asymptomatic patients with reduced
left ventricular ejection fractions. N Engl J Med. 1992; 332277 : 685–91.
3 Pfeffer MA, Braunwald E, Moye LA et al. Effect of captopril on
mortality and morbidity in patients with left ventricular dysfunction
after myocardial infarction. Results of the survival and ventricular
enlargement trial. N Engl J Med1992; 332277 : 669–77.
4 Mancini GB, Schulzer M. Reporting risks and benefits of therapy by
use of the concepts of unqualified success and unmitigated failure:
applications to highly cited trials in cardiovascular medicine.
Circulation1999; 9999 : 377–83.